Cancer metastasis via the blood stream can be modeled as a problem of fluid-solid interaction with multiple bodies (cells) of different masses, momentum, and physical qualities, in motion, within a complex flow field. The Four Dimensional Biopsy Center (4DB) utilizes physics-based measurements, mathematical modeling and numerical simulation to empirically characterize actual human cancer patient samples, with a goal of establishing a highly predictive model of human cancer cell behavior that will fundamentally alter our current understanding of the mechanisms of cancer metastasis. Extensive empirical measurements and analyses will be performed on a coherent set of samples from human cancer patients. Samples will consist of cells from primary tumors, locoregional metastases, and circulating tumor cells (CTCs) over time, all collected from the same patient. Additionally, a second cohort of samples will consist of CTCs from a large set of patients, stratified by tumor type and cancer stage. These sample sets will be analyzed in parallel by three independent Research Projects (RPs), producing orthogonal measures of identical phenomena, and delivering the variables and the correlations on the space and time dimension of epithelial cancers. The three Research Projects (RP) are: RP1 Cytophysics, which determines the physical and mechanical properties of cancer cells;RP2 Topology, which measures the topology, morphology, and travel group strategies of cancer cells;and RP3 Dynomics, which characterizes the genomics and transcriptomics of cancer cells. With assessment of depth, breadth, and fidelity thus assured, the measurements will be empowered by analyses of other parameters, including standard pathologic and clinical patient information. This extensive amalgamation of data, based primarily on physics investigations and mathematical theory, but informed by strategic patient sampling and clinical information, will be processed by advanced statistical analysis and mathematical modeling, to enable a highly predictive simulation of cancer spread that will revolutionize our understanding of metastasis. The 4DB Center will also serve to disseminate information, education, and training to a new generation of cancer physicists;a generation that will implement the power of physics to conquer the problems of cancer.

Public Health Relevance

Deaths due to metastatic cancer continue to mount. Despite decades of effort, this set of diseases continues to evade our best therapeutic efforts and our best biologic investigations. The Four Dimensional Biopsy Center (4DB) takes cancer research in a new direction by pinning the metastasizing cancer cell directly in the spotlight of powerful physics and mathematics based measurements and modeling.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZCA1-SRLB-9 (O1))
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Ogunbiyi, Peter
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Scripps Research Institute
La Jolla
United States
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Phillips, Kevin G; Kuhn, Peter; McCarty, Owen J T (2014) Physical biology in cancer. 2. The physical biology of circulating tumor cells. Am J Physiol Cell Physiol 306:C80-8
Jones, Casey M; Baker-Groberg, Sandra M; Cianchetti, Flor A et al. (2014) Measurement science in the circulatory system. Cell Mol Bioeng 7:1-14
Dago, Angel E; Stepansky, Asya; Carlsson, Anders et al. (2014) Rapid phenotypic and genomic change in response to therapeutic pressure in prostate cancer inferred by high content analysis of single circulating tumor cells. PLoS One 9:e101777
Phillips, Kevin G; Baker-Groberg, Sandra M; McCarty, Owen J T (2014) Quantitative optical microscopy: measurement of cellular biophysical features with a standard optical microscope. J Vis Exp :
Rodriguez-Lee, Mariam; Kuhn, Peter; Webb, David R (2014) Advancing cancer patient care by integrating circulating tumor cell technology to understand the spatial and temporal dynamics of cancer. Drug Dev Res 75:384-92
Totonchy, Jennifer E; Clepper, Lisa; Phillips, Kevin G et al. (2014) CXCR7 expression disrupts endothelial cell homeostasis and causes ligand-dependent invasion. Cell Adh Migr 8:165-76
Carlsson, Anders; Nair, Viswam S; Luttgen, Madelyn S et al. (2014) Circulating tumor microemboli diagnostics for patients with non-small-cell lung cancer. J Thorac Oncol 9:1111-9
Bethel, Kelly; Luttgen, Madelyn S; Damani, Samir et al. (2014) Fluid phase biopsy for detection and characterization of circulating endothelial cells in myocardial infarction. Phys Biol 11:016002
Bazhenova, Lyudmila; Newton, Paul; Mason, Jeremy et al. (2014) Adrenal metastases in lung cancer: clinical implications of a mathematical model. J Thorac Oncol 9:442-6
Baker-Groberg, Sandra M; Phillips, Kevin G; McCarty, Owen J T (2013) Quantification of volume, mass, and density of thrombus formation using brightfield and differential interference contrast microscopy. J Biomed Opt 18:16014

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